Peripheral nerve involvement in Krabbe disease

In this issue of Neurology, Siddiqi et al.¹ present two studies on peripheral neuropathy in Krabbe disease (KD): the first a survey of electrodiagnostic findings in 34 patients, and the second on the effect of hematopoietic stem cell transplantation on peripheral nerve function.² These studies gain in clinical significance because of the recent development of technology for newborn screening for KD,³ and its impending implementation in at least one state, combined with the proposal to perform hematopoietic stem cell transplantation in asymptomatic infants with KD.^4,5

KD, also referred to as globoid leukodystrophy, is an autosomal recessive disorder caused by a defect in the gene that codes for glucocerebrosidase beta-galactosidase, with an estimated incidence of 1:100,000.⁶ KD is characterized by the accumulation of globoid multinucleated cells, demyelination, loss of oligodendrocytes, and gliosis in the CNS. The defective enzyme also degrades galactosylsphingosine (psychosine). Psychosine, normally present in low concentration, is increased 100-fold and may a play a major role in pathogenesis.⁷ The rapidly progressive early infantile form is the most common phenotype, thought to affect 90% of all patients with KD. Later onset childhood, juvenile, and adult forms also occur and may be have been underdiagnosed in the past, a point of increasing importance in view …